The basic objectives of this proposal are to make creative contributions to the total synthesis of naturally occurring substances possessing clinically significant biological activity. Targets for total synthesis include the potent antibiotics naphthyridinomycin, saframycin, macbecin, rosaramycin, josamycin, tylosin, and the Beta-lactams thienamycin and aphalosporin. Recently developed chiral enolate technology will be applied to enantioselective approaches to the construction of many of the listed target structures. Naphthyridinomycin, saframycin and macbecin all exhibit significant antitumor activity and rosaramycin (and related macrolides) and thienamycin are clinically valuable broad-spectrum antibiotics which are active against both gram-positive and gram-negative bacteria.